Induction of apoptosis in human microvascular endothelial cells by divalent cobalt ions. Evidence for integrin-mediated signaling via the cytoskeleton

Wound healing following implantation is characterized by an acute inflammat ory reaction and a subsequent reorganizing phase in which angiogenesis is i nvolved. Endothelial cells (EC) participate in both inflammation and angiog enesis. Thus, the effects on functions of EC exerted by implanted materials could affect the progression of wound healing. The corrosion of metallic i mplants can cause high concentrations of heavy metal ions in the peri-impla nt tissues. The purpose of the present study was to test the effects of pos sible corrosion products on the function and viability of human EC in vitro . Long-term exposure of EC to CoCl2 and NiCl2 (3 days, 0.7 mM) leads to a d ecrease of cell number and changes in cellular morphology. However, the mor phological changes between CoCl2- and NiCl2-treated cells differ significan tly. The changed morphology of CoCl2-treated EC and the fragmented DNA patt ern indicates apoptosis. Nickel-treated cells demonstrated necrosis. The ac tivity of integrins was tested by an assay of cellular adhesion on collagen -coated surfaces. It was shown that the number of adherent cells significan tly decreased upon exposure to CoCl2. Our studies suggest that induction of cell death in EC upon exposure to CoCl2 could be attributed to impaired in tegrin signaling, which leads to a damaged cytoskeleton and culminates in a poptosis. (C) 2001 Kluwer Academic Publishers.